Leukemia is a name for a group of diseases that are cancers of the marrow and blood. The two major groups are lymphatic, and myeloid leukemia. Both groups are considered as either acute or chronic depending on various factors. Also included are lymphoid leukemias. Leukemias can thus be divided into four main types: acute lymphocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia and chronic myelogenous leukemia. Acute and chronic leukemias are usually studied as groups separated by the cells which are affected.
These heterogeneous groups are usually considered together and are considered as a group of diseases characterized by infiltration of the bone marrow and other tissues by the cells of the hematopoetic system. The infiltration is called neoplastic, meaning new growth of cells, but all of the cells seen in the marrow, and peripheral circulation in leukemia are normal in a normal bone marrow, except for one structure, seen in myelocytic leukemia called Auer rods. These structures are repeated in this kind of leukemia, and are unknown as to structure, and relationship to any other material.
The majority of patients with leukemia are not cured with standard chemotherapy. There is no therapy that is considered standard of care in patients with relapsed acute lymphocytic leukemia. Because the median age is 70 years in the U.S., the majority of patients are not eligible for allogeneic stem cell transplantation, which is the only known cure for patients with relapsed or refractory acute leukemia. Although there are various investigational agents available, the response rates are small, duration of response short and adverse events sometimes unacceptable. Thus, there is an unmet need for new agents in this group of patients who are otherwise managed with supportive care only.
An adult human has about 7000 white blood cells per microliter (μl) of blood. Of those white cells, about 65 percent are granulocytes (about 4500/μl), about 30 percent are monocytes (about 2100/μl) and about five percent are lymphocytes (about 350/μl) [Geyton, Textbook of Medical Physiology, Seventh ed., W. B. Saunders Co., Philadelphia (1986)]. The above cell numbers are, of course, generalized average values, and granulocyte counts for normal patients typically range from about 2000 to about 7000 cells/μl.
Chronic myelogenous leukemia (CML), also known as chronic granulocytic leukemia (CGL), is a neoplastic disorder of the hematopoietic stem cell. In its early phases, this disease is characterized by leukocytosis, the presence of increased numbers of immature granulocytes in the peripheral blood, splenomegaly and anemia. These immature granulocytes include basophils, eosinophils, and neutrophils. The immature granulocytes also accumulate in the bone marrow, spleen, liver, and occasionally in other tissues. Patients presenting with this disease characteristically have more than 75,000 white blood cells per microliter, and the count may exceed 500,000/μl. Cytologically, CML is characterized by a translocation between chromosome 22 and chromosome 9. This translocation juxtaposes a purported proto-oncogene with tyrosine kinase activity, a circumstance that apparently leads to uncontrolled cell growth. The resulting translocated chromosome is sometimes referred to as the Philadelphia chromosome.
CML accounts for about 20 percent of all leukemias in the United States. About 15 new cases per million people are reported each year, leading to about 3,000 to 4,000 new cases per year. The disease is rare in humans below age 45, rises rapidly to age 65, and remains high thereafter. The median life span of patients with chronic myelogenous leukemia from the time of diagnosis is approximately four years.
Patients with chronic CML have usually been treated with alkylating agents such as busulfan or by treatment with hydroxyurea. In recent years treatment with α-interferon has been used.
About 60 to 80 percent of patients with CML develop a blast crisis. This blast crisis represents a manifestation of acute leukemia. The presence of certain markers on the blast cells sometimes suggests a lymphoid origin of these cells during the blast crisis. Chemotherapeutic agents used for the treatment of the blast crisis are the same as those used for the treatment of other acute leukemias. However, these drug therapies of the blast crisis stage of CML are even less successful than are the treatments of other acute leukemias.
Chronic lymphocytic leukemia (also known as “chronic lymphoid leukemia” or “CLL”), is a leukemia of the white blood cells (lymphocytes) that affects a particular lymphocyte, the B cell, which originates in the bone marrow, develops in the lymph nodes, and normally fights infection. In CLL, the DNA of a B cell is damaged, so that it cannot fight infection, but grows out of control and crowds out the healthy blood cells that can fight infection.
CLL is an abnormal neoplastic proliferation of B cells. The cells accumulate mainly in the bone marrow and blood. Although not originally appreciated, CLL is now thought to be identical to a disease called small lymphocytic lymphoma (SLL), a type of non-Hodgkin's lymphoma which presents primarily in the lymph nodes. The World Health Organization considers CLL and SLL to be “one disease at different stages, not two separate entities”. [Harris et al., (1999) “World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997”, J. Clin. Oncol. 17(12):3835-3849.]
CLL is a disease of adults. Most (>75%) people newly diagnosed with CLL are over the age 50, and the majority are men. In the United States during 2007, it is estimated there will be 15,340 new cases diagnosed and 4,500 deaths [National Cancer Institute. “Chronic Lymphocytic Leukemia (PDQ) Treatment: General Information”, Retrieved on 2007-09-04] but because of prolonged survival, many more people are living with CLL.
Most people are diagnosed without symptoms as the result of a routine blood test that returns a high white blood cell count, but as it advances, CLL results in swollen lymph nodes, spleen, and liver, and eventually anemia and infections. Early CLL is not usually treated, and late CLL is treated with chemotherapy and monoclonal antibodies. Survival varies from 5 years to more than 25 years. It is now possible to diagnose patients with short and long survival more precisely by examining the DNA mutations, and patients with slowly-progressing disease can be reassured and may not need any treatment in their lifetimes [Chiorazzi et al., (2005) N. Engl. J. Med. 352(8):804-815].
Acute lymphocytic leukemia (ALL) is also referred to as acute lymphoblastic leukemia and acute lymphoid leukemia. About 5,430 people in the United States are expected to be diagnosed with ALL in 2008 [The Leukemia & Lymphoma Society web site updated Jul. 14, 2008]. It is the most common type of leukemia in children under age 15. The risk of getting ALL increases in people ages 45 and older. However, people can get ALL at any age. Most children with ALL are cured of their disease after treatment.
ALL is said by the The Leukemia & Lymphoma Society to start with a change to a single cell in the bone marrow. The exact genetic changes that cause a normal cell to become an ALL cell are being studied. Few factors have been associated with an increased risk of developing ALL. Exposure to high doses of radiation therapy used to treat other types of cancer is one known risk factor. Other possible risk factors are continually under study. ALL is said not to be contagious [The Leukemia & Lymphoma Society web site updated Jul. 14, 2008].
Aplastic anemia is a condition in which bone marrow does not produce sufficient new cells to replenish blood cells. Aplastic anemia typically results from injury to blood stem cells. Normal blood stem cells divide and differentiate into all blood cell types. Thus, when blood stem cells are injured, there is a reduction in red blood cells, white blood cells, and platelets.
Aplastic anemia can be caused by chemotherapy, drug therapy to suppress the immune system, radiation therapy, toxins such as benzene or arsenic, drugs, pregnancy, and disorders present birth. When the cause is unknown, it is then referred to as idiopathic aplastic anemia. The disease can be acute or chronic and usually gets worse unless the cause is removed.
The term ‘aplastic’ means the marrow suffers from an aplasia that renders it unable to function properly. Anemia is the condition of having reduced hemoglobin or red cell concentration in the blood. Typically, anemia refers to low red blood cell counts, but aplastic anemia patients have lower counts of all three blood cell types: red blood cells, white blood cells, and platelets, or pancytopenia.
This disease is characterized by the following symptoms: 1) a low red blood cell count (anemia) leads to fatigue and weakness; 2) a low white blood cell count (leukopenia) leads to frequent or severe infections; 3) a low platelet count (thrombocytopenia) that can result in easy bruising, nose bleeds, bleeding of the gums, and bleeding of internal organs. Other symptoms include shortness of breath during physical activity, rapid heart rate, and rash. Identifying assays include one or more of the following: a complete blood count (CBC) that shows low hematocrit and hemoglobin levels (anemia); a reticulocyte count that is low; a low platelet count; a low white blood cell count; and a bone marrow biopsy that shows very few cells.
Rifampicin, or rifampin, below, is a drug whose
use has been approved for infections caused by a great number of infectious agents. Its action appears to be an effect on DNA-dependent RNA polymerase activity of bacterial infections. Rifampicin is useful for gram negative bacteria such as Neiseria meningitides, and M. tuberculosis. 
Rifampicin is also effective against intracellular bacterial pathogens. Rifampicin is particularly effective against intracellular organisms in the genus of Ehrlich/Anaplasma, for which it appears to be the only effective antibiotic, with tetracycline being less effective and bacteriostatic.